Postherpetic neuralgia (PHN) is a complication of herpes zoster (commonly known as shingles) in which pain persists for more than 3 months after resolution of the rash (three months is the most commonly identified duration, although definitions of duration for postherpetic neuralgia vary from more than 1 month to less than 6 years). Postherpetic neuralgia affects between 10% to 15% of people who have herpes zoster and increases with age, affecting up to 70% of those infected who are more than 70 years old (Davies, P. S. and Galer, B. S., Drugs 2004, Vol. 64, No. 9, pp. 937-47; Dubinsky, R. M. et al., Neurology 2004, Vol. 63, No. 6, pp. 959-65; Kost, R. G. and Staus, S. E., N. Eng. J. Med. 1996, Vol. 335, No. 1, pp. 32-42). Elderly patients tend to have more severe and longer lasting postherpetic neuralgia.
Despite the numerous compounds available for treating postherpetic neuralgia, 40% to 50% of postherpetic neuralgia patients do not respond to any treatment (Rowbotham, M. C. and Petersen, K. L., Pain 2001, Vol. 93, pp. 1-5). Antiviral therapy for acute herpes zoster has been shown to accelerate clearing of the rash, but a recent meta-analysis showed that it does not reduce the likelihood of the development of postherpetic neuralgia (Chen, N et al., Cochrane Database Syst. Rev. 2009 Apr. 15(2):CD006866). Antivirals also have no demonstrable benefit after the rash has cleared and are of no use once postherpetic neuralgia is established. Tricyclic antidepressants were the first analgesic agents that showed efficacy in randomized controlled trials of postherpetic neuralgia, and, subsequently, anticonvulsant agents, strong opioids, and topical analgesics have also demonstrated efficacy.
A topical patch containing 5% lidocaine, a nonselective sodium channel blocker (LIDODERM®, Endo Pharmaceuticals Inc), was approved by the United States (US) Food and Drug Administration (FDA) for the treatment of PHN. In 2004, a subcommittee of the American Academy of Neurology determined that there was solid Class I evidence of efficacy for the lidocaine patch in postherpetic neuralgia (Dubinsky et al. 2004). The lidocaine patch, if perhaps less effective than other approved treatments such as gabapentin and pregabalin (Dworkin, R. H. et al., Neurology 2003, Vol. 60, No. 8, pp. 1274-83), is considered highly efficacious in postherpetic neuralgia, although there have been no head-to-head comparisons with other agents and the number-needed-to-treat (NNT) varies from study to study (Davies and Galer 2004). The safety and tolerability of the lidocaine patch has probably contributed most to its widespread use in postherpetic neuralgia. Safety and the reduced risk of drug-drug interactions (DDIs) with a topical formulation are particularly relevant, given the elderly age of most patients affected by postherpetic neuralgia and their need for concomitant medications.
The difficulty of treating postherpetic neuralgia adequately, with many patients refractory to available therapies, indicates that there is an ongoing medical need for new treatment options providing effective topical pain relief of postherpetic neuralgia with a good safety profile with minimal or negligible or systemic exposure of the therapeutic agent.